Liver
regeneration
has been well studied with hope of discovering strategies to improve
liver
disease outcomes. Nevertheless, the signals that initiate such
regeneration
remain incompletely defined, and translation of mechanism-based pro-regenerative interventions into new treatments for hepatic diseases has not yet been achieved. We previously reported the isoform-specific regulation and essential function of zinc-dependent histone deacetylases (Zn-HDACs) during mouse
liver
regeneration
. Those data suggest that epigenetically regulated anti-proliferative genes are deacetylated and transcriptionally suppressed by Zn-HDAC activity or that pro-regenerative factors are acetylated and induced by such activity in response to partial hepatectomy (PH). To investigate these possibilities, we conducted genome-wide interrogation of the
liver
histone acetylome during early PH-induced
liver
regeneration
in mice using acetyL-histone chromatin immunoprecipitation and next generation DNA sequencing. We also compared the findings of that study to those seen during the impaired regenerative response that occurs with Zn-HDAC inhibition. The results reveal an epigenetic signature of early
liver
regeneration
that includes both hyperacetylation of pro-regenerative factors and deacetylation of anti-proliferative and pro-apoptotic genes. Our data also show that administration of an anti-regenerative regimen of the Zn-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) not only disrupts gene-specific pro-regenerative changes in
liver
histone deacetylation but also reverses PH-induced effects on histone hyperacetylation. Taken together, these studies offer new insight into and suggest novel hypotheses about the epigenetic mechanisms that regulate
liver
regeneration
.

Liver
regeneration
has been well studied with hope of discovering strategies to improve
liver
disease outcomes. Nevertheless, the signals that initiate such
regeneration
remain incompletely defined, and translation of mechanism-based pro-regenerative interventions into new treatments for hepatic diseases has not yet been achieved. We previously reported the isoform-specific regulation and essential function of zinc-dependent histone deacetylases (Zn-HDACs) during mouse
liver
regeneration
. Those data suggest that epigenetically regulated anti-proliferative genes are deacetylated and transcriptionally suppressed by Zn-HDAC activity or that pro-regenerative factors are acetylated and induced by such activity in response to partial hepatectomy (PH). To investigate these possibilities, we conducted genome-wide interrogation of the
liver
histone acetylome during early PH-induced
liver
regeneration
in mice using acetyL-histone chromatin immunoprecipitation and next generation DNA sequencing. We also compared the findings of that study to those seen during the impaired regenerative response that occurs with Zn-HDAC inhibition. The results reveal an epigenetic signature of early
liver
regeneration
that includes both hyperacetylation of pro-regenerative factors and deacetylation of anti-proliferative and pro-apoptotic genes. Our data also show that administration of an anti-regenerative regimen of the Zn-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) not only disrupts gene-specific pro-regenerative changes in
liver
histone deacetylation but also reverses PH-induced effects on histone hyperacetylation. Taken together, these studies offer new insight into and suggest novel hypotheses about the epigenetic mechanisms that regulate
liver
regeneration
. PMID:25482284

According to ethical intuitionists, basic moral propositions are self-evident. Robert Audi has made significant progress articulating and defending this view, claiming that an adequate understanding of a self-evident proposition justifies rather than compels belief. It is argued here that understanding a proposition cannot justify belief in it, and that intuition, suitably understood, provides the right sort of justification. An alternative account is offered of self-evidence based on intuition rather than understanding, and it is concluded that once we have an adequate understanding of a self-evident proposition, we can see that it does no distinctive epistemic work. It merely reports that intuition is doing some significant epistemic work. Since the very idea of self-evident moral propositions is so controversial, and self-evidence does no significant epistemic work, ethical intuitionists should drop this notion from their moral epistemology. All they need are intuitive propositions and our intuition of these.